Effect of ethanolic fruit extract of xylopia aethiopica (Dunal) A. Rich (Annonaceae) and Xylopic Acid on Reproductive Function in Male Rats

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Xylopia aethiopica (African guinea pepper) is used mainly as a spice, postpartum tonic and to induce postpartum placental discharge by traditional birth attendants (TBA) and to enhance male fertility across the West African Sub-region especially Ghana and Nigeria. Despite of its frequent and regular use, no attempt has been made to scientifically examine the effects of the spice on reproduction as well as the toxicological profile. The present study was thus undertaken to evaluate the effect of 70% alcoholic extract of the fruits of Xylopia aethiopica and its major constituent, xylopic acid on steroid hormones, spermatogenesis and testicular histology as well as the toxicity profile in male. Extract of Xylopia aethiopica was administered (30, 100 and 300 mg/kg p.o) to different groups of male rats for sixty days. Blood samples were collected 24 hours after the last treatment by cardiac puncture for haematology parameters and for enzyme and other biochemical assays. Oral administration of the extract produced significant (p<0.001) increases Hb, total white blood cells and neutrophil in a dose dependent fashion. It however did not affect RBC, and HCT. The extract also caused a significant increase in serum total protein, albumin, globulin, HDL and total cholesterol levels as well as indirect and total bilirubin dose dependently while decreasing serum ALT. It did not however have a significant effect on Renal function test (urea and creatinine). The present finding indicates that Xylopia aethiopica fruit has immune boosting properties. In order to evaluate the effect of 70% alcoholic extract of Xylopia aethiopica on reproductive function of adult male rat, ethanolic fruits extract of X. aethiopica was administered orally to groups of male Sprague Dawley rats at the doses of 30, 100 and 300 mg/kg for 60 days. The reproductive organ weights, change in animal body weight, caudal epididymal sperm count, motility and viability, histology of testes and androgenic hormonal levels were evaluated. Increase in body weight as well as weight of testis and epididymis and a significant increase in caudal sperm count was noticed. Histological sections of testis exhibited spermatogenesis. Extract treatment also induced significant increase in serum testosterone and luteinizing hormone levels. The studies clearly reveal androgenic activity of the extract and its effects on hypothalamic pituitary gonadal axis. To evaluate the effect of xylopic acid on serum sex hormone levels and spermatogenesis in male rats, Male Sprague Dawley rats were divided into four groups of six animals each. Group I served as the control and were given distilled water (vehicle for the XA). Groups II, III and IV rats were given XA orally at the dose of 10, 30 and 100 mg kg−1 respectively for 28 days. Blood was collected from the saphenous veins of animals on day 7 of the treatment and on day 28 after which the rats were euthanized to remove testes and other organs for biochemical and histological analysis. Xylopic acid did not cause any changes in body weight, but significantly decreased testicular and epididymal weight (P < 0.01). Sperm motility, viability, and epididymal sperm counts of rats treated with Xylopic acid for 28 days were significantly reduced (P < 0.01). Serum testosterone levels were significantly reduced (P < 0.01). Untreated females mated by treated males exhibited significant decrease in fertility index in dose-dependent manner. The testes of the treated rats also exhibited some degree of oxidative stress as measured by the level of MDA and glutathione peroxidase activity in the testis. There were varying degrees of damage to the seminiferous tubules. Reversal of these changes, however, occurred after two weeks of recovery. In conclusion, Xylopic acid may possess reversible antifertility activity as well as spermatotoxic properties the mechanism of which may involve direct effect on mature spermatozoa and germ cells in the testes as a result of oxidative stress causing defective sperm cells and hence reduce fertility. To characterize potential anti-androgenic properties of xylopic acid and to elucidate the possible mechanism of the antifertility activity of xylopic acid in rats, xylopic acid was administered to orchidectomized immature rats following the Hershberger assay protocol. This evaluates the ability of a chemical to elicit biological activities consistent with androgen agonists, antagonists or 5α-reductase inhibitors. Thirty male Sprague-Dawley rats (42 days old, weighing about 60-70 g) which were either orchidectomized or sham operated. At 11 days post-castration the rats were weighed and assign to five treatment groups. The animals were treated daily for 10 days and the weight of the animals taken daily. On the day after the last treatment the rats were necropsied to isolate organs and tissues for study of androgenic or anti-androgenic effects. The endpoints evaluated were the growth/body weight, and weight of the seminal vesicles plus coagulating glands with fluid, ventral prostate, levator ani plus bulbocavernosus muscle, glans penis, Cowper’s glands (bulbourethral glands), and liver all without fixation. Xylopic acid exhibited anti- androgenic activity similar to cyproterone acetate, an anti-androgenic agent by decreasing the weight of the accessory sex organ. In conclusion whereas the crude extract possesses fertility enhancing properties, the pure acid exhibits anti-androgenic properties.
A Thesis submitted to the School of Graduate Studies, Kwame Nkrumah University of Science and Technology, Kumasi, in partial fulfilment of the requirements for the Degree of Doctor of Philosophy in Pharmaceutics, January-2012